Ammonium Chloride → N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a cold (−30° C.), stirred suspension of ((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl)triphenylphosphonium bromide (376 mg, 0.55 mmol) in dry tetrahydrofuran (10 mL) is added lithium hexamethyldisilazane in THF (0.42 mL of 1.33 M, 0.55 mmol). The reaction mixture is stirred for 30 min, cooled to −78° C., and treated with a solution of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehyde (9) (130 mg, 0.50 mmol) in 5 mL of tetrahydrofuran. After 60 min, the solution is warmed to ambient temperature, stirred for 10 min, and treated with saturated ammonium chloride solution. The aqueous phase is extracted with t-BuMeO (2×10 mL), and the combined organic layers dried and concentrated. The residue is purified by silica gel chromatography (elution with t-BuMeO/hexane mixture) to give 190 mg (65%) of N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (10) as white amorphous solid.

Provenance & Evidence